Inflammation is a defensive mechanism in the pathophysiology of many chronic diseases, including cancer, gastrointestinal problems, arthritis, cardiovascular disease, chronic wounds, and lesions, which may lead to death worldwide. Research over several decades has resulted in many non-steroidal anti-inflammatory drugs (NSAIDs), but they are associated with adverse drug reactions. As a result, the need for new anti-inflammatory drugs has significantly increased. A key target of NSAIDs, cyclooxygenase (COX) catalyses the synthesis of prostanoids, a broad family of arachidonic acid metabolites including prostacyclin, thromboxane, and prostaglandins. The inhibition of COX is implicated in gastrointestinal toxicities and ulceration. The inducible isoform of COX-2 is quickly expressed in various cell types in response to proinflammatory chemicals, cytokines, growth factors, and diseases related to inflammation. Thus, avoidance strategies for the nonselective COX inhibition and targeting COX-2 selectively are studied for COX-2 inhibitors for the treatment of inflammation, free from side effects. The scaffolds present in known inhibitors are important to achieve the goals. Pyrazole is the most noticeable and familiar heterocyclic scaffold. The prominent anti-inflammatory properties of pyrazole derivatives make them an important family of drugs. This article provides a comprehensive overview of new pyrazole derivatives synthesis and inhibitory activity against COX-2 for the past 5 years. The structure-activity relationship (SAR) and docking insights from this article could be helpful for the medicinal chemist in the development of next-generation COX-2 inhibitors.
Nath et al. (2026) studied this question.